The sarcoplasmic reticulum in muscle is homologous to the endoplasmic reticulum found in most cells and forms a series of sleevelike segments around each myofibril. At the end of each segment there are two enlarged regions, known as lateral sacs, that are connected to each other by a series of smaller tubular elements. The lateral sacs store the calcium that is released following membrane excitation. A separate tubular structure, the transverse tubule (T-tubule), crosses the muscle fiber at the level of each A-I junction, passing between adjacent lateral sacs and eventually joining the plasma membrane. The lumen of the T-tubule is continuous with the extracellular fluid surrounding the muscle fiber. The membrane of the T-tubule, like the plasma membrane, is able to propagate action potentials. Once initiated in the plasma membrane, an action potential is rapidly conducted over the surface of the fiber and into its interior by way of the T-tubules.
A specialized mechanism couples T-tubule action potentials with calcium release from the sarcoplasmic reticulum. The T-tubules are in intimate contact with the lateral sacs of the sarcoplasmic reticulum, connected by structures known as junctional feet or "foot proteins." This junction involves two integral membrane proteins, one in the T-tubule membrane, and the other in the membrane of the sarcoplasmic reticulum. The T-tubule protein is a modified voltage-sensitive calcium channel known as the dihydropyridine (DHP) receptor (so named because it binds the class of drugs called dihydropyridines). The main role of the DHP receptor, however, is not to conduct calcium, but rather to act as a voltage sensor. The protein embedded in the sarcoplasmic reticulum membrane is known as the ryanodine receptor (because it binds to the plant alkaloid ryanodine). This is a large molecule that not only constitutes the foot proteins but also forms a calcium channel. During a T-tubule action potential, charged amino acid residues within the DHP receptor protein induce a conformational change, which acts via the foot proteins to open the ryanodine receptor channel. Calcium is thus released from the lateral sacs of the sarcoplasmic reticulum into the cytosol, activating cross-bridge cycling. The rise in cytosolic calcium in response to a single action potential is normally enough to saturate all troponin binding sites on the thin filaments.
A contraction continues until calcium is removed from troponin, and this is achieved by lowering the calcium concentration in the cytosol back to its prerelease level. The membranes of the sarcoplasmic reticulum contain primary active-transport proteins (Ca2+-ATPases) that pump calcium ions from the cytosol back into the lumen of the reticulum. Calcium is released from the reticulum upon arrival of an action potential in the T-tubule, but the pumping of the released calcium back into the reticulum requires a much longer time. Therefore, the cytosolic calcium concentration remains elevated, and the contraction continues for some time after a single action potential. To reiterate, just as contraction results from the release of calcium ions stored in the sarcoplasmic reticulum, so contraction ends and relaxation begins as calcium is pumped back into the reticulum. ATP is required to provide the energy for the calcium pump, and this is the third major role of ATP in muscle contraction.